Some of the main research objectives are: (1) To determine the mechanism of activation by the catecolamine alpha receptor. Is there a specific 2nd messenger? (2) To determine directly whether phosphodiesterase activation by insulin is due to phosphorylation of the enzyme. What is the kinase and how is it activated by the hormone? (3) Purification and characterization of hepatic gycogen synthetase. What is the role of cyclic AMP-dependent and independent kinases in control of its activity? (4) Continued study will be made of cAMP-dependent protein kinase particularly the role of the membrane bound enzyme. (5) What is the nature and physiological role, if any, of cGMP-dependent protein kinase? (6) It is hoped to purify protein phosphatase(s) and characterize them using well characterized substrates. Is there metabolic control exerted on the phosphatase? (7) What is the chemical nature and physiological role of the sea urchin egg factor which raises sperm levels of cAMP? (8) Mechanisms (?phosphorylation) controlling glucose transport will be looked for. (9) Phosphodiesterases and their control will be studied. (10) cAMP-dependent phosophorylation of pyruvate kinase in vivo and in vitro will be examined. (11) What is the molecular mechanism of action of acetyl choline? BIBLIOGRAPHIC REFERENCES: J. H. Exton, T. B. Miller, Jr., S. C. Harper and C. R. Park, Carbohydrate metabolism in perfused livers of adrenalectomized and steroid-replaced rats. Am. J. Physiol. 230, 163-170, l976. T. M. Lincoln, C.L. Hall, C. R. Park and J. D. Corbin, Guanosine 3':5'-cyclic monophosphate binding proteins in rat tissues, Proc. Nat. Acad. Sci, U.S.A. 73(8) in press, l976.